1,4-cyclohexanedione mono-2,2-dimethyl trimethylene ketal is an intermediate in the synthesis of (+)-R-2,3,4,9-tetrahydro-3-(methylamino)-1H-carbazole-6-carboxamide butanedioate, frovatriptan, which is a serotonin (5-HT) receptor agonist and is known as anti-migraine drug. A few synthetic methods for 1,4-cyclohexanedione mono-2,2-dimethyl trimethylene ketal are known in the art.
Journal of Synthetic Communications 9(2), 123–127 (1979) disclosed a process for the preparation of 1,4-cyclohexane dione mono-2,2-dimethyl trimethylene ketal using Birch reduction of 4-methoxy phenol with lithium and ammonia in presence of ethanol to yield 4-methoxy-3-cyclohexene-1-ol, which is further reacted with neopentyl glycol using PTSA in benzene medium gave 2,3-dimethyl-1,3-dipropylene ketal of 4-hydroxycyclohexanone. Oxidation of the resulting ketal with pyridinium chlorochromate yields the 1,4-cyclohexanedione mono-2,2-dimethyl trimethylene ketal. Journal of Synthetic Communications, 14 (1), 39–44 (1984) disclosed a process for preparation of 1,4-cyclohexanedione mono-2,2-dimethyl trimethylene ketal that includes continuous extraction of an aqueous solution of 1,4-cyclohexane dione containing 2,2-dimethyl-1,3-propane diol in molar excess and sulfuric acid as the catalyst to afford the 1,4 cyclohexanedione mono-2,2-dimethyl trimethylene ketal. Nevertheless, there is still a need for an improved process suitable for a commercial scale production of 1,4-cyclohexanedione mono-2,2-dimethyl trimethylene ketal
and structurally related compound.